MEMBERS OF THE BOARD OF TUTORS

Fraenkel, Ernest, Ph.D.

My laboratory analyzes high-throughput data in order to improve our understanding of the regulatory mechanisms of the cell in normal and diseased states. We are currently working on two main problems: understanding transcriptional regulation and analyzing models of neurodegenerative diseases.While the genomes of many organisms have been sequenced, the sequences alone do not reveal the regulatory program that governs gene expression. To identify the regulatory signals that are encoded in the sequence data, we have generated an initial map of the transcriptional regulatory sites throughout the genome of S. cerevisiae. This map was derived by computational analysis of binding data from genome-wide chromatin immunoprecipitation experiments and sequence data from related yeast species. With knowledge of these regulatory sites, we can begin to model how changes in the binding of transcription factors specify variations in gene expression. We plan to adapt the techniques that we developed for analysis of transcription in yeast to analyze the more complicated problem of transcriptional regulation in higher eukaryotes. Recently, our collaborators have developed models for the neurodegenerative diseases Parkinson+s and Huntington+s by expressing fragments of the proteins alpha-synuclein and huntingtin in yeast. These protein fragments cause the yeast cells to develop a phenotype that is similar to that of diseased neurons. We are analyzing a variety of high-throughput data from these model systems to discover the molecular basis for the toxicity of these proteins.